Surgical implant for marking soft tissue

ABSTRACT

An implantable tissue marker device is provided to be placed in a soft tissue site through a surgical incision. The device can include a bioabsorbable body in the form of a spiral and defining a spheroid shape for the device, the spiral having a longitudinal axis, and turns of the spiral being spaced apart from each other in a direction along the longitudinal axis. A plurality of markers can be disposed on the body, the markers being visualizable by a radiographic imaging device. The turns of the spiral are sufficiently spaced apart to form gaps that allow soft tissue to infiltrate between the turns and to allow flexibility in the device along the longitudinal axis in the manner of a spring.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/456,435, filed Apr. 26, 2012, entitled “Surgical Implant for MarkingSoft Tissue,” which application is incorporated herein by reference inits entirety.

This application incorporates by reference United States patentpublication no. 2009-0024225-A1, entitled “Implant for TargetingTherapeutic Procedure,” filed on Jul. 16, 2008, which application isincorporated herein by reference in its entirety.

This application incorporates by reference United States patentpublication no. 2011-0004094 A1, entitled “Bioabsorbable Target forDiagnostic or Therapeutic Procedure,” filed on May 28, 2010, whichapplication is incorporated herein by reference in its entirety.

BACKGROUND

Two trends have become significant in driving the delivery of medicaltreatments: First, treatments, be they drugs, energy or surgery, aremoving towards local and more precise (i.e., focused) delivery, andsecond, treatments are being tailored and optimized for each patientbased on their specific anatomy, physiology and disease features. Thesedirections both are designed to minimize the likelihood of adverseeffects from the therapies as well as provide a more patient-specifictreatment, which may improve disease-free survival rates and/orimprove/decrease local recurrence of disease.

Many of these trends have been adopted in the surgical environment wherelarge, open surgical procedures have been and continue to be replaced bylaparoscopic techniques and other minimally invasive procedures. Drugtherapies are moving toward more localized delivery as well, such astreatments that are placed directly at or near the treatment site (e.g.,drug eluting stents and GLIADEL wafers for brain tumors). Untilrecently, the desire to do the same in radiation therapy has beenhampered by inadequate technology for focused delivery. However,significant progress in the delivery of radiation to a more localizedregion of treatment (i.e., localized radiation delivery) has becomepopularized in the field of brachytherapy, a subspecialty of radiationoncology, most notably used in the treatment of prostate, breast, andgynecologic cancer patients. As an example, in breast brachytherapy, theradiation source is temporarily inserted into one or more catheters thatare temporarily placed and held within the breast at the site where thetumor has been removed. The prescribed dose of radiation is calculatedand customized for each patient, and is delivered directly to the areaat highest risk of local recurrence. This system allows for moreaccurately directed treatment, which is effectively delivered from the“inside out.” This approach has gained popularity because it offers anumber of benefits to patients undergoing treatment for breast cancerincluding delivery of the equivalent dose of radiation in a shortertimeframe (normally 5-7 days vs. daily for up to 6 weeks) and deliveryto a smaller volume of the breast tissue (i.e., accelerated and smallervolume treatments). Thus, by delivering a customized and focused amountof radiation, the therapeutic advantage is maintained while thepotential damage to surrounding normal tissues is minimized.

Although brachytherapy is gaining acceptance throughout the world,external beam radiation therapy (EBRT) remains the most common method ofdelivery for radiation therapy. EBRT is used in the treatment of manydifferent types of cancers, and can be delivered before, during and/orafter surgery. In addition, chemotherapy is often utilized inconjunction with radiation therapy. EBRT is delivered to cancer patientsas either the first line of therapy (for non-resected cancers) or as ameans of maximizing local control of the cancer following surgicalremoval of the tumor. The radiation is meant to help “sterilize” thearea of tumor resection in an effort to decrease the potential forrecurrent disease.

In EBRT, one or more beams of high energy x-rays are aimed at the partof the body needing treatment with radiation. A linear accelerator(often called a linac) produces the beams and has a collimator thathelps to shape the beams as they exit the linac. It is very common fortwo or more beams to be used, each of which is delivered from differentdirections around the area of the tumor or the site of tumor resection.Often, in planning the delivery of the radiation, the beams are directedso that they will intersect at the tumor site, thereby focusing thehighest dose of radiation at the most critical area. In this manner, thenormal tissues surrounding the target are exposed to lower amounts ofradiation. At the same time, the exact target site receives a moreprecise and accurately delivered dose, since the sum of the treatmentbeams are greatest at the directed tumor target. The tumor target volumeis the region delineated by the radiation oncologist using CT scans (orother imaging methods such as ultrasound or MRI) of the patient. Thetumor target volume and radiation dose prescription parameters areentered into a treatment planning computer. Treatment planning software(TPS) then produces a plan showing how many beams are needed to achievethe radiation oncologist's prescription dose, as well as the size andshape of each beam.

Historically, EBRT is practiced by dividing the total radiation doseinto a series of smaller more tolerable doses which are delivered to thepatient sequentially. Dosage is typically limited by the tolerance ofnormal tissues surrounding the site to be treated. Hence, often, theradiation therapy is continued until side effects become intolerable tothe patient. The target volume, in which it is desired to deliveressentially 100% of the prescribed radiation dose, has historically beendefined as the tumor (the gross tumor volume, or GTV) plus a surroundingvolume of tissue margin that may harbor remaining microscopic tumorcells (the clinical target volume, or CTV). Another margin ofsurrounding normal tissue is added to the CTV to account for errors inpositioning of the patient for therapy and movement of the tumor siteboth during a fraction and between fractions.

In the treatment of breast cancer, the complete course of EBRT isdivided (fractionated) into numerous small, discrete treatments each ofwhich is referred to as a “fraction”. A typical prescribed dose of 60Gray (Gy) is fractionated into 30 daily treatments of 2 Gy per day.During a fraction, the treatment beam may be “on” for ˜1 minute. Thus,to achieve the full treatment dose, the radiation therapy is typicallydelivered 5 days per week over a 6 week period. In the treatment ofbreast, lung, chest and upper abdominal (e.g. pancreatic) cancers thedelivery of radiation therapy must take into consideration the changesin tissue position during respirations which may alter the position ofthe target tissue.

Another common procedure in which EBRT is used is whole breastradiation, typically used as a radiation therapy regimen followingsurgical lumpectomy as treatment for breast cancer. In this form oftherapy, the entire breast is irradiated multiple times in small dosefractions over a course of treatment that typically lasts about 1-2months. In addition to these whole breast doses, most patients receivean additional “boost” dose that is given to the area immediatelysurrounding the lumpectomy cavity, as this region is suspected to be ofhigher risk of recurrence. Often there is difficulty and uncertainty inidentifying the exact tissue location of this post-lumpectomy tissueregion. As a result of this uncertainty, larger tissue volumes thanwould otherwise be necessary are defined for boost treatment to ensurethat the correct “high risk” target tissue indeed receives the boostdose. In addition, as the boost target is smaller than the whole breastthat was treated, the actual “targeted” boost tissue volume is smallerthan the whole breast target and can be more difficult to specificallytarget or define for treatment.

In the last few years, the treatment planning software and linearaccelerator technology have dramatically improved in their ability toshape the radiation therapy beams to better avoid nearby sensitivestructures (also known as “organs at risk” or non-target tissues). Thelatest treatment planning software allows the radiation oncologist andmedical physicist to define the volume of tissue to be treated using CTscans and provide therapy constraints (e.g., minimum radiation doseinside the target volume, maximum radiation dose to structures nearbytarget volume). The software then automatically computes the beam anglesand shapes in a process called inverse treatment planning. This processcan be even further refined using a technique called Intensity ModulatedRadiation Therapy (IMRT) which shapes the beam of radiation. Anotherfeature of the newer linear accelerators is a type of radiographic(and/or ultrasonic) imaging that is used to better position the patientand his/her tumor for more accurate targeting of the treatment beams.This latter method is called Image Guided Radiation Therapy, or IGRT.

Both IMRT and IGRT techniques use numerous, smaller and more preciselyshaped beams that intersect at the target volume. IGRT differs from IMRTin at least one important aspect—imaging prior to each fraction is usedto reduce positioning errors and make sure the treatment beam isproperly targeted. Typically, IGRT uses bony anatomy (e.g., pelvic bonesfor prostate patients) for radiographic targeting and soft tissueinterfaces (e.g., prostatic capsule and bladder wall) for ultrasoundtargeting. Rarely, implanted radio-opaque markers (e.g., VISICOIL) havebeen used to facilitate targeting for IGRT. However, using a singlemarker device that defines in a 3 dimensional/volumetric manner thelimits or margins of treatment has not yet been accomplished. In thetreatment of breast cancer specifically, some clinicians have attemptedto help delineate the margins of the lumpectomy cavity by usingradio-opaque markers such as surgical clips placed at the time ofsurgery. This, in theory, may help the radiation oncologist in treatmentplanning, however, often these clips are inaccurate in their placement,have a tendency to migrate postoperatively (e.g., due to their mobilityand other healing and scarring issues), and may be confused with othersurgical clips used for haemostatic control during surgery. Tissuechanges and scarring can markedly affect the position of these clips,thus leading to the possibility of inaccurate targeting of theradiation. In addition, these markers have not been used withsignificant success for targeting in the newer delivery methods, such asfor each fraction or each beam of every fraction as is done in IGRT.

IMRT uses a special type of collimator, a multi-leaf collimator (MLC)that changes the shape of the beam during each fraction to modulate or“sculpt” the radiation dose to more closely fit the actual target volumeshape in three dimensions. Linear accelerators equipped with MLCs cancontrol the size and shape of the beam to within a few millimetersaccuracy. However, to best take advantage of their precision, the tissuetarget needs to be accurately defined in 3 dimensions.

IGRT is a relatively new option on linear accelerators, however many newlinacs are available today that have on-board imaging capability viamega-voltage (MV) or kilo-voltage (KV) x-rays/fluoroscopy. The on-boardimaging capability can also be retrofitted to existing equipment.On-board imaging is a technical capability that has been introduced intothe newest linac product lines by major manufacturers of linearaccelerators (e.g., Varian Medical Systems, Elekta, Tomotherapy, Accurayand Siemens). While the technology made by these companies provides thepossibility of performing better targeting for external beam radiationtherapy, the targets (e.g., bony anatomy) are inadequate in order toachieve a precise and accurate target region for precision treatment ofa specific tissue region, often because of inaccuracies associated withcorrelating bony anatomy to the adjacent soft tissue target region.

As described above, targeting the external beam radiation therapyaccurately requires one to point out the target using markers known as“fiducials.” These fiducial markers have different radiographicproperties than that of the surrounding tissue (e.g., bone, and softtissue). To date, this has been accomplished using radio-opaque markers(e.g., permanently implanted foreign bodies). Alternatively, Patrick andStubbs described a device and method for shaping and targeting EBRTusing a temporarily implanted balloon catheter (U.S. Pat. No.7,524,274). This device and method required implantation of a foreignbody whose removal necessitated a second medical/surgical procedure.There is clinical evidence suggesting that the implantation andirradiation of an area of the breast surrounding an implanted ballooncan result in long-standing complications such as persistent seroma(collection of fluid within the breast that may become infected). Thereare a number of clinical difficulties that preclude use of aballoon-type device as a realistic/good option to define a tissue targetfor radiation. For example, a balloon device may interfere with the EBRTtreatment since the balloon and its contents may affect the transmissionof the EBRT, and therefore may affect the dose of radiation reaching thetarget tissue. In addition, the balloon may inhibit tissue growth backinto the cavity during the healing process, which can lead to irregularand unsightly scarring, which is particularly undesirable followingbreast surgery for cancer. The balloon can be uncomfortable to thepatient during the course of treatment, and thus, use of a balloon-typedevice for targeting radiation therapy has not been useful in theclinical domain.

Hence, the need exists for a better fiducial marker device and methodfor more accurately defining the target tissue volume and providing animageable target for the external beam treatments, without requiringsubsequent removal.

SUMMARY

The invention described herein uses implantable devices that can allowfor more accurate targeting of external beam radiation to the region oftissue that is to be treated. The devices provide a 3-dimensional targetor group of targets that is used to focus the radiation therapytreatment beams directly onto the targeted tissue—for example, thetissue surrounding a tumor resection cavity. The device may be formed ofan absorbable material that is implanted intraoperatively during thesame surgical procedure as the tumor resection and requires no secondprocedure to remove (it is resorbed in situ in the patient's body).

In a first aspect, an implantable fiducial tissue marker device isprovided for placement in a soft tissue site through an open surgicalincision. The device includes a bioabsorbable body formed whose outerregions define a peripheral boundary of the marker device. A pluralityof visualization markers are secured to the body so that visualizationof the marker device using medical imaging equipment will indicate the3-dimensional location of the tissue site. The device is alsoconformable to the adjacent soft tissue and its peripheral boundary isable to be penetrated by adjacent soft tissue during its use.

In specific embodiments, the bioabsorbable body is in the shape of aspiral where the spiral has a longitudinal axis and turns of the spiralare spaced apart from each other in a direction along the longitudinalaxis. The peripheral boundary of the device can have a shape selectedfrom the group consisting of spherical, scalene ellipsoid, prolatespheroid, and oblate spheroid shape. The device can also have a northpolar region and a south polar region at opposed ends of thelongitudinal axis. A strut can further be connected between the northpolar region and the south polar region. The strut can include a slidingelement to allow the spiral body to be compressed in the manner of aspring.

Visualization markers can be attached to the body in the north polarregion and/or the south polar region. A plurality of visualizationmarkers can also be attached to the body about an equatorial region ofthe substantially spheroid device. In one embodiment, at least fourvisualization markers are attached to the body about its equatorialregion. At least some of the visualization markers can be radio-opaqueclips. The radio-opaque clips can be attached to the body usingpreformed holes in the body into which the clips can be pressed andattached.

In a further aspect, a method for fabrication of a tissue marker deviceis provided. The device can be fabricated using injection molding toform a body made of a bioabsorbable polymer in a planar configuration.The body can be heat formed so that the body is reconfigured from aplanar configuration to a three dimensional configuration.

In specific embodiments, fabrication of the device can include formingpockets or through-holes in the body during injection molding andattaching visualization markers to the pockets or through-holes. Theinjection molded body can include north and south polar regions, witheach polar region including a polar extension that is directed toward aninterior of the device. Fabrication can further include connecting astrut to the polar extensions. The strut can be slideably connected toat least one of the polar extensions. Also, two or more separate partscan be connected to achieve a finished product.

In a still further aspect, an implantable tissue marker device isprovided to be placed in a soft tissue site through a surgical incision.The device can include a bioabsorbable body in the form of a spiral anddefining a spheroid shape for the device, the spiral having alongitudinal axis, and turns of the spiral being spaced apart from eachother in a direction along the longitudinal axis. A plurality of markerscan be disposed on the body, the markers being visualizable by aradiographic imaging device. The turns of the spiral are sufficientlyspaced apart to form gaps that allow soft tissue to infiltrate betweenthe turns and to allow flexibility in the device along the longitudinalaxis in the manner of a spring.

In specific embodiments, the device can have a spring constant in thedirection of the longitudinal axis between about 5 and 50 grams permillimeter. The bioabsorbable body can include opposed polar regionsalong the longitudinal axis. Markers can be placed in each of the polarregions. A plurality of markers can also be placed along an equatorialregion of the body.

In one embodiment, at least four markers are placed along the equatorialregion.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be more fully understood from the following detaileddescription taken in conjunction with the accompanying drawings:

FIGS. 1A and B illustrate a spiral implant device of the invention;

FIG. 2 illustrates a spiral implant device of the invention having acentral strut;

FIG. 3 illustrates a spiral implant device of the invention having acentral strut, with marker clips secured within the spiral body;

FIGS. 4 A and B illustrate stages of fabrication for a spiral implantdevice of the invention;

FIG. 5 illustrates a stage of fabrication for a spiral implant device ofthe invention;

FIG. 6 illustrates a further stage of fabrication for a spiral implantdevice of the invention;

FIG. 7 illustrates an alternate embodiment of a spiral implant device ofthe invention;

FIGS. 8A and B illustrate an additional embodiment of an implant deviceof the invention;

FIGS. 9A, B, C and D illustrate an additional embodiment of an implantdevice of the invention;

FIGS. 10A, B, C, and D illustrate an additional embodiment of an implantdevice of the invention;

FIG. 11 illustrates an embodiment of an implant device that has beenplaced in a surgical resection cavity;

FIG. 12 illustrates another embodiment of an implant device that hasbeen placed in a surgical resection cavity;

FIG. 13 illustrates another embodiment of an implant device that hasbeen placed in a surgically created breast lumpectomy cavity;

FIG. 14 illustrates another embodiment of an implant device that hasbeen placed in a surgical resection cavity;

FIG. 15 illustrates an additional embodiment of an implant device of theinvention;

FIGS. 16A, B, and C illustrate sizing tools with corresponding spiralimplant devices of the invention;

FIGS. 17A and B illustrate additional 2-dimensional embodiments of animplant device of the invention;

FIG. 18 illustrates an alternative 2-dimensional embodiment of animplant device of the invention; and

FIG. 19 illustrates an idealized tumor resection cavity in soft tissueas is known in the prior art.

DETAILED DESCRIPTION

The invention described herein uses implantable devices that can allowfor more accurate targeting of external beam radiation to the region oftissue that is to be treated. The devices provide a 3-dimensional targetor group of targets that is used to focus the radiation therapytreatment beams directly onto the targeted tissue—for example, thetissue surrounding a tumor resection cavity. The device may be formed ofan absorbable material that is implanted intraoperatively during thesame surgical procedure as the tumor resection and requires no secondprocedure to remove (it is resorbed in situ in the patient's body).

In one embodiment, the invention includes a spiral, bioabsorbablesurgical implant 10 (illustrated in FIG. 1A in a spherical configurationand in FIG. 1B in an ellipsoid configuration) with at least one integraltargeting marker component that is visible by means of clinical imaging(radiographic, ultrasonic, MRI, etc.). In many embodiments, the implant10 has a relatively non-complex peripheral shape that can facilitateeasy target delineation, such as spheres, ellipsoids, or cylinders. Inthis way, the implant (and/or the markers affixed thereto) can bevisualized, and its contours (and thus the contours of the target tissueto be treated—typically marginal regions surrounding an excised tumor)can be readily determinable. Treatment can then be applied to the targettissue. The size and shape of the implant can be varied to correspond tothe most common resection cavity sizes and shapes. The device may beflexible and may be in its predetermined shape before placement andalthough it may tend toward that predetermined shape after implantation,the implant is subject to the forces applied to it by the patient'stissue and hence its shape is able to deform and conform to the adjacenttissue as well. Similarly, the device may become integrated into thesurrounding tissue as it is absorbed by the body, leaving the markers inproximity of the previously excised tumor for future clinical tracking.The device can be sized as needed for a particular surgery, however,preferred sizes range from about 2 cm to about 6 cm in longest diameter.

As illustrated in FIGS. 1A and 1B, the surgical implant 10 of theinvention is formed as a spiral. The spiral nature can permit theimplant 10 to be more flexible than it otherwise might be. For example,the implant 10 can flex along its axis 34 in length in the manner of anextension or compression spring or bend along its axis 34 in the mannerof bendable coil spring. In addition, the lack of continuous walls canallow the implant to flex in directions other than along its axis. Suchflexibility can allow for the target tissue, and the cavity into whichthe implant 10 is placed, to flex as the patient moves, making theimplant more comfortable for the patient. In addition, the open natureof the spiral can allow tissue growth and insinuation into the cavitywhich may reduce the incidence or effects of seroma, and in someinstances may be able to reduce the volume of the target to beirradiated.

The shape of the illustrated implant 10 in FIG. 1A is spherical,however, the implant could also be made in other shapes, such as afootball-shaped ellipsoid (illustrated in FIG. 1B) or cylindrical. Asused herein, the term “spheroid” is expressly intended to include bothspherical and ellipsoid shapes for the implant 10—as such, both theembodiments of FIG. 1A and FIG. 1B are spheroid. The choice of shape maydepend on the shape and nature of the cavity into which the implant 10is being placed. In the case of a lumpectomy cavity commonly related tobreast cancer, a relatively spherical shape is a common choice.

While the implant 10 could have any shape, regular shapes that arereadily modeled by external radiation beam treatment devices arepreferred. Such shapes can include spherical, scalene ellipsoid, prolatespheroid, and oblate spheroid shapes. Again, the use of the term“spheroid” herein is intended to include all of these spherical andellipsoid shapes. Other regular shapes such as cylinders or squarescould also be used, however, sharp corners might make it more difficultto shape radiation doses to the target tissue. In general, the implant10 can have polar regions with an open framework extending between thepolar regions. Such an open framework would include a body 12 thatprovides sufficient stability to mark the boundaries of a tumorresection cavity, while having sufficient gaps 14 in the body to allowtissue around the cavity to infiltrate the device. In this illustratedembodiment, the shape of the implant 10 is created by a continuous orone-piece body 12 that is formed into a spiral having gaps 14 betweenthe turns of the spiral, the overall spiral having a spherical shapewith polar regions 16, 18. In each polar region 16, 18, there is anextending portion 20, 22, which, in this embodiment, extends inwardtoward the center of the spherical shape.

In addition, the open framework can be designed to provide specificlevels of flexibility. As noted elsewhere herein, the illustrated spiraldesign acts as a spring. By varying the rigidity of the material makingup the body 12, and/or by varying the thickness of body 12, a springconstant for the device 10 can be varied to achieve a desiredflexibility. That is, by design the spring constant may provide acertain amount of force in order to keep the markers in their positionalong the margins of the cavity, but allow sufficient flexibility forpatient comfort and to minimize scarring, therefore the device 10 can beoptimized for its intended purposes. Preferred embodiments for use intreating breast cancer include those having a spring constant (denotedas “k”, in units of grams/mm) between about 5 and 15 grams permillimeter axial deflection for the 4 cm diameter devices (morepreferably 8-12 g/mm), between about 10 and 25 g/mm axial deflection forthe 3 cm diameter devices (more preferably 15-20 g/mm), and betweenabout 25 and 70 grams/mm axial deflection for the 2 cm devices (morepreferably 30-50 g/mm). The inventors have discovered that it can bebeneficial to have higher k values for smaller diameter devices.

Typical sizes of the device range from 2-6 cm in equatorial diameter and2-8 cm in length. It is useful for the clinician to have a range ofproduct diameters and lengths to choose from to provide the optimalconfiguration for a given patient.

The implant 10 is preferably able to be visualized on a medical imagingapparatus so that it can be used for targeting therapy. In theillustrated embodiment, visualization characteristics may be enhanced byproviding by visualization markers in the form of radio-opaque clips 24,26, 28 that provide high contrast visibility on imaging devices. In theillustrated configuration, a first clip 24 is provided at the “northpole”, a second clip 26 is provided at the “south pole”, and four clips28 are distributed substantially around the equatorial region of thespherical implant 10. This clip array permits a specific outlining, orin other words a characterization of the extent of the borders of thetissue cavity in all 3 dimensions, and in this embodiment, the xy, zyand xz planes. More or fewer clips can be used to provide more detailedor less detailed tissue site identification, as needed. Given theflexibility and shape of implant 10 as described and illustrated, clipsare preferentially provided at the two poles and also in some numberdistributed substantially about the equator, or elsewhere along itsspiral length. In this manner, even where the spherical implant flexesin vivo, or the tissue around the cavity moves or flows, the 3dimensional shape of the tissue region can be identified, based on thelocation of the clips. It is worth noting that, with currently availablehigh resolution imaging systems, including CT, mammography, MRI, andultrasound, the presence of the clips may not be necessary to image theimplant and hence image the surrounding soft tissue. The mere presenceof the bioabsorbable body, which need not contain air gaps in the bodymaterial, can in some cases, be sufficient to delineate or demarcate thedesired tissue location.

As illustrated, each of the north and south pole clips 24 and 26 islocated within the respective polar region extension 20, 22. Each of theclips is secured to the body material. In this embodiment, the polarclip is configured as a wire element that is folded onto itself, withthe wire ends slightly flared prior to assembly. During assembly theclip is inserted into a cylindrical hole in the polar region. The flaredends of the clip serve as a unidirectional gripping element thatprevents the polar clip from backing out of the hole once it isinstalled. The equatorial clips may be secured to body 12 using pocketsor through-holes 30 created in regions 32 that exist for the purpose ofproviding the clips with a location to provide secure attachment. Theseequatorial clips 28, also made from metal wire can be attached byproviding that the middle portion of the clip resides within the hole30, and the end portions of the clip curve around the region 32, asillustrated, to fix them securely to the body 12 in the shape of a “D”.This D shape facilitates the differentiation of these marker elementsfrom the polar clips and from conventional haemostatic clips that may beused to control bleeding during the surgical procedure. In an alternatemethod of securing the clips, as can be seen in FIG. 7, the peripheralclips 28 may be placed in a lumen of a long spiral segment 12 ofbioabsorbable tubing. The clips can be made from any biocompatible,radio-opaque material, such as titanium, stainless steel, gold orcomposite polymer materials (e.g., made with carbon or Barium Sulfate)having the desired visualization characteristics.

As noted above, the bioabsorbable body 12 itself may have visualizationproperties in addition to or in place of the clips 24, 26, 28. That is,the characteristics of the body material, or a coating on the body, maybe chosen so that the body itself may be visualized on an imaging deviceand used for targeting. In particular, the body 12 may have radiodensity(or magnetic spin recovery when using MRI) that is different from thetissue surrounding the cavity into which the implant 10 is placed forthe purpose of making the body 12 visible on an imaging device. Forexample, breast tissue can present values ranging from −140 to 50 on theHounsfield scale—a linear transformation of the original linearattenuation coefficient measurement to one in which the radiodensity ofdistilled water at standard pressure and temperature (“STP”) is definedto have a Hounsfield number of zero, while the radiodensity of air atSTP is defined to have a Hounsfield number of −1000. Details forcreating this contrast in an implantable device can be found inpublished U.S. patent application no. 2011-0004094 A1, filed on May 28,2010 and entitled Bioabsorbable Target for Diagnostic or TherapeuticProcedure, which is hereby incorporated by reference. The density of thebody 12, however, should not be so high as to impart significantattenuation of the radiation beams or imaging artifact, which may resultin clinically compromised target delineation or altering the dosedelivered by a clinically significant amount. Where clips or othermarkers are used, the density of the body 12 may in some cases beindistinguishable from that of the surrounding tissue for visualizationand treatment purposes. In addition, the body 12 material and/or theclips may have a roughened or faceted surface finish to enhance theultrasound imaging ability of the visualization device.

Various materials that could be used to construct body 12 include knownbioabsorbable materials such as polyglycolic acid (PGA, e.g., Dexon,Davis & Geck); polyglactin material (VICRYL, Ethicon); poliglecaprone(MONOCRYL, Ethicon); and synthetic absorbable lactomer 9-1 (POLYSORB,United States Surgical Corporation) and polydioxanone. Other materialsinclude moldable bioabsorbable materials such as poly lactic acid (PLA),including Poly L-lactic acid (PLLA) and various PLA/PGA blends. Theseblends can include caprolactone, DL lactide, L lactide, glycolide andvarious copolymers or blends thereof. Mixtures of any of theaforementioned materials can also be used, as required. The materialscan be modified, by cross-linking, surface texturing, or blended withone another to control degradation rates over varying lengths of time,after which they are substantially or completely resorbed. Anothermanner in which degradation rates can be altered is by subjecting themto additional radiation in the dose ranges typically used for radiationsterilization. For example, subjecting the device to e-beam radiation inthe dose range of 25 to 40 kiloGray (kGy) is typical for an adequate,validated sterilization cycle. However, subjecting the device to anadditional 25 to 75 kGy can be useful to accelerate the in-situdegradation rate without significantly adversely affecting thefunctional short-term mechanical properties of the device. Inembodiments that are used for radiation therapy targeting, themechanical properties of body 12 are maintained for a long enough fortreatment to take place. In some cases, the body 12 lasts long enoughfor tissue to infiltrate the cavity such that the position of thevisualization markers is fixed within the tissue. Also, the material ispreferably rigid enough for the overall effect of the spiral shape tobehave in a resiliently deformable manner after implantation.

A cross sectional shape of the body 12 may also be selected to achievethe desired spring constant and absorbance parameters. In general, body12 may have a cross section that is circular, oval, ovoid, cruciform, orrectangular. Other shapes can also be used.

As illustrated in FIGS. 2 and 3, the implant 10 may also have a strut 36extending in the direction of its longitudinal axis 34. In particular,the strut 36 can be connected between the north and south polarextensions 20, 22. In a preferred embodiment, the strut 36 providesstructural support, but also allows some translation of at least onepolar region toward or away from the other polar region with respect toan unflexed position of the spiral body 12. In many situations in use,the spiral body 12 will flex in the manner of a spring and particularlyin compression. Strut 36 allows compression along the longitudinal axis,but may also provide a stop to prevent over compression of the spiralbody 12.

In one embodiment, the strut 36 is a tubular element that fits over eachof extensions 20, 22 and maintains a fixed relationship with oneextension while sliding with respect to the other extension. Thisconfiguration would allow the spiral body 12 to be compressed until anedge of the tubular strut 36 contacted one of the polar regions 16, 18which would act as a stop. In another embodiment, the strut 36 couldslide with respect to each of the extensions 20, 22. In a still furtherembodiment, the strut 36 could comprise two overlapping tubes that slidewith respect to each other in the longitudinal direction and opposedends of such a strut could be fixed to the polar extensions 20, 22. In anon-sliding embodiment, the strut 36 could be fixed to both extensions20, 22 with no internal sliding.

The present inventors have also developed a preferred fabrication methodfor forming the body 12. In a fabrication step, illustrated in FIGS. 4and 5, body 12 is formed into two substantially planar, opposed, andconnected spirals. Body 12 could be extruded and then heat-formed asshown in FIG. 5 (the shaping of a thermoplastic material by heating itand causing a permanent deformation (such as bending) that remains afterthe material cools) into the desired shapes described above, however,such handling of bioabsorbable is difficult and repeatability in formingthe shapes can be challenging. In a preferred embodiment, this firststep is carried out by injection molding as shown in the spiral forms ofFIGS. 4AB and C. This shape can be molded from a simple two part moldwithout the need for side pulls, which allows for repeatability yetmodest tooling costs. In addition, the molded part allows for moresurface detail, for example at the two ends of the part—rounded endswith pockets for visualization markers or fabrication fixtures may beincorporated into the design, as illustrated for example in FIG. 4A.Pockets for additional visualization markers can be molded along thelength of the body at appropriate intervals, as shown in FIG. 4B.

The entire body 12 may at this stage be substantially planar tofacilitate injection molding. When we say substantially planar we meanof a configuration that is able to be injection molded without the needfor side pulls, or that can be die cut from a sheet form of the bodymaterial. Visualization markers may also be attached to body 12 at thisstage where the body is substantially planar, as shown in FIG. 4C, whichis conducive to automated assembly methods.

In the embodiment of FIG. 4, left spiral 40 includes a north polarextension 42, while opposed right spiral 44 includes a south polarextension 46. A connecting segment 48 connects the two opposed spirals.

FIG. 5 illustrates a similar embodiment to FIG. 4, but lacking polarextensions, which could be heat-formed later, or omittedcompletely—especially if a central strut is not desired. A subsequentstep in a fabrication process results in a device that is illustrated inFIG. 6, where the configuration of FIG. 5 has been heat-formed so thatone spiral 40 is located above the other spiral 44 so that the spiralsshare a common longitudinal or central axis. For the embodiment of FIG.5, either spiral could go over the other. For the embodiment of FIG. 4,however, having polar extensions 42, 46 that have a directional element,the left spiral 40 preferably would be placed on top of the right spiral44 so that the polar extensions extend toward each other—that is, towardthe center of the finished spiral implant.

During the heat-forming process the centers of the overlapping spirals40, 44 can be reformed, (e.g., over a mandrel) so that body 12 takes thegeneral shape of a sphere. The final shape of the final implant can bedetermined during this heat forming step. For example, heat forming thecenters to project out of plane less than the full radius distance of asphere shape will result in a flattened sphere. Heat forming beyond thefull radius distance will elongate the sphere to a football shape asshown in FIG. 1B. Forming one spiral side farther from the midline thanthe other will result in an egg shape. In embodiments in which thecentral strut is desired, the strut may next be added. To facilitateeven and repeatable reforming, the body 12 may be placed around aspheroid forming mandrel and heated to form the final desired shape. Toenhance fabrication consistency, the forming mandrel may have channelsalong its surface to hold the part in a given position during theheat-forming process.

FIG. 7 shows a device formed as shown in FIG. 6, with the addition ofmarker clips which are placed at desired locations along the centrallumen of the body of the device. These marker clips may be placed in thelumen before or after final heat forming into the final spheroid spiralshape.

FIGS. 8 through 10 all describe alternate embodiments where thebioabsorbable marker component (e.g. body 12) is initially formed in arelatively planar configuration (e.g. for ease of injection molding) andthen the component is subsequently heat-formed into its final spheroidor other three dimensional configuration. Note that the embodiments havean open architecture to maximize the opportunity for tissue ingrowth,tissue movement, tissue approximation and/or fluid communication acrossthe peripheral boundary of the marker device. The open architecture alsoallows for the passage of suture around a portion of the device by theclinician to help secure the device to adjacent tissue (e.g., chestwall) to further immobilize the device. The marker devices describedherein comprise a resilient framework of bioabsorbable elements withlocations for periodic secure attachment of radiodense marker elements(e.g., titanium wire) along the periphery of the device. The flexibilityand conformability of the device allows for device deformation forincreased comfort and conformance to the surrounding tissue in which thedevice is placed. When we use the term “peripheral boundary” of themarker device, we are referring not only to the boundary edge of themarker device itself but also to the “empty space” regions in betweenthe portions of the marker device that are generally consistent with theperimeter of the device.

FIG. 8A shows an alternate embodiment of the device 10 a where thebioabsorbable component is molded in a planar, cross-like configurationwith a body having four branches, 12 a, 12 b, 12 c, and 12 d. Eachbranch includes a feature 30 a for attaching a marker about an equatorof the device, while one branch 12 a includes at its end a feature 30 afor attaching a north pole marker and the center of the cross includes afeature 30 a for attaching a south pole marker. FIG. 8B shows the deviceafter the component has been heat formed (e.g., around a sphericalmandrel with recessed grooves) to generate a spherical device 10 ahaving north and south polar regions 16, 18. Other shapes describedherein could also be formed in this manner, as well as, shapes formedwith more or fewer branches. In general, the number of branches will bebased upon the width of the branches, the desired size of gaps betweenthe branches in the finished device (and thus the device's “openness”),and the number of markers desired about the equator of the device.

Another embodiment of the device is shown in FIGS. 9A through 9D. Afirst portion 52 of a bioabsorbable component 10 b is molded in the formas shown in FIG. 9A having three petal-like branches 12 e, 12 f, and 12g. The three cylindrical protrusions 54 in the center of each petal-likeelement contain a radiopaque marker (not shown) such as a titaniumwireform for use as equatorial markers. The central cylindricalprotrusion 56 comprises a fastening means (e.g., press-fit or matingthreads) for assembling the device and can also include a radiopaquemarker (not shown). The component 52 can subsequently be heat-formedaround a curved mandrel to create a component as illustrated in FIG. 9B.A central axial extension 58 can be added to two portions 52 to createan assembled bioabsorbable device 10 b as shown as FIG. 9C, which is theexploded view of the completed device that is shown in FIG. 9D.

FIGS. 10A to 10D show yet another embodiment of the device 10 c wherethe bioabsorbable component is molded in an alternating continuousfilament 12 h configuration forming four loops 62 a-62 d in the form ofa cross with each loop being open towards the center. Each loop 62 a-62d includes a feature 30 to allow placement of equatorial markers 28.Loop 62 a includes a feature 64 for placement of a north polar marker24, while a feature 66 for placement of a south polar marker 26 islocated at the center of the device 10 c between any two loops. FIG. 10Bshows the device 10 c after the component has been heat formed (e.g.,around a spherical mandrel with recessed grooves) and with the markers24, 26, 28 added. The forming mandrel not only creates a spherical shapeof the final configuration but the recessed grooves in the mandrel alsohelp space apart the filaments to create a relatively even spacing ofthe bioabsorbable filament (and thus equal spacing of gaps or openingsto allow tissue infiltration) along and throughout the spherical surfaceof the device. FIG. 10C and FIG. 10D show top and side views,respectively of the device 10 c embodiment shown in FIG. 10B.

These types of devices can typically be used by surgeons who do notactively reapproximate the tissue (e.g. lumpectomy) cavity that theyhave created, as has been previously described herein. In addition, thisdevice can also be used by surgeons who choose to surgicallyreapproximate at least a portion of the breast tissue surrounding thelumpectomy cavity. This reapproximation, sometimes called cavityclosure, is typically accomplished (e.g. in the growing field ofoncoplastic surgery) by suturing the breast tissue on either side of thelumpectomy cavity and drawing the tissue together (See FIG. 11) prior toskin closure. FIG. 11 shows a spiral marker 10 as described in FIG. 1that has been placed in a lumpectomy cavity 72 of a patient's breast. Ascan be seen in the figure, the cavity is in the process of being closedwith suture 74 and one can appreciate the tissue infiltrating 76 intothe interstices of the spiral device 10. The open architecture of thedevice allows the tissue to flow or otherwise move within the peripheralboundary of the device as the tissue is pulled together and secured bysuture. This device thus allows the surgical cavity site (and itsmargins) to be marked in a 3 dimensional fashion for subsequent imagingeven though the lumpectomy cavity itself may be surgically altered ornaturally altered in original size and/or shape. The lumpectomy cavitymay be naturally (i.e. passively) altered in size or shape by partiallyor totally collapsing on itself or some cases by expanding due to seromabuildup within the lumpectomy cavity in the post-surgical period.

FIG. 12 shows a similar device 10 in another lumpectomy cavity 72 andone can appreciate the degree to which the surrounding tissue hasinfiltrated 76 within and flowed around the marker 28. Thus, these openarchitecture 3-dimensional tissue markers as described herein, allow theclinician to demarcate the closed and/or collapsed cavity with a levelof 3-dimensional accuracy that has not previously been possible.

FIG. 13 shows device 10 after placement in a lumpectomy cavity 131 atthe time of surgery via a standard surgical incision 132. Because of theopen architecture of the device 10, the breast and fatty tissues 133 atthe margin of the lumpectomy cavity are able to naturally infiltrateacross the peripheral boundary (dotted line 134) of the tissue markerdevice. The peripheral boundary 134 of the device is defined as thecontinuous overall surface shape that is defined by the outer regions orperipheral surface elements (for example 135) of the device. For thedevice 10 shown in FIG. 13, the peripheral boundary is an ovoid surface,a view of which is shown in this figure as an oval dotted line 134.Cavity boundary tissue can be seen to insinuate, penetrate, and/or flowbetween and around the elements of the device, thereby crossing theperipheral boundary of the device at for example, tissue locations 136and 137.

The method of use for example, in a breast lumpectomy procedure is asfollows: a lumpectomy cavity is created by surgically removing breasttissue via a skin incision (which may be minimally invasive, e.g. viatunneling from the areola), the cavity is sized using a sizer or othersizing method (e.g. direct examination of the lumpectomy specimen orcavity), the appropriately sized 3 dimensional open architecturebioabsorbable tissue marker is placed directly into the lumpectomycavity via the surgical incision causing the breast tissue at the marginof the cavity to actively (e.g. via suture closure) or passivelyinsinuate or otherwise move across the peripheral boundary of the tissuemarker device, and then the wound or skin is closed in standard surgicalfashion.

In yet another alternative method of use, the device is used as abovebut with the added step of passing some suture around one or moreportions of the device and then passing the suture through adjacenttissue to tether or otherwise further secure the device to the adjacenttissue.

In some instances, the degree of tissue insinuation within theboundaries of the marker device (and hence the cavity) can be fairlylimited. This instance can be appreciated in FIG. 14, where a markerdevice 10 of the type described in FIG. 1 has been placed in alumpectomy cavity 72 of a patient's breast. One can see that in thisapproach, only a modest amount of tissue has infiltrated between thespiral elements and a significant portion of the original cavity remainsfree of tissue, with the marker device (including the marker clips)delineating the margins of the lumpectomy cavity.

FIG. 15 shows an alternate embodiment 10 d where a mesh-like structurecomprised of biodegradable filaments 82 is formed into a cavity-sizedopen-architecture shell-like structure with marker clips 84 secured atvarious peripheral locations of the structure. In one embodiment, themarker clips are still placed at the north and south poles and with fourmarkers placed around the equator. This construction maximizes theoverall diameter of the device while using a minimum mass ofbiodegradable material. The mesh-like structure (woven or braidedfilaments, or die-cut sheet) is also conformable yet still maintains a3-dimensional volumetric characterization of the adjacent tissue as itresides within the cavity. The marker clips reside at the periphery ofthe device and hence optimizes visualization of the boundaries of thesurgical cavity. The degree of tissue infiltration across the boundaryof the device perimeter can be varied by the chosen gap size (e.g., from1 mm to 10 mm). All versions within this gap size range are of anopen-architecture design where fluids (e.g. blood, seroma, lymphaticfluid) can freely pass across the peripheral boundary of the deviceafter implantation.

A method according to the invention for treating these and othermalignancies begins by surgical resection of a tumor site to remove atleast a portion of the cancerous tumor and create a resection cavity asillustrated in FIG. 18. As illustrated, an entry site or incision 102 iscreated in patient 100 in order to remove tissue and create a cavity104. Although FIG. 7 visually represents the surgical resection cavityin concept, it is important to note that most cavities are not thatsimplistically configured in the 2-8 week postoperative period that theyare most likely to be visualized in the clinical imaging environment.For example, Landis et al (“Variability among breast radiationoncologists in delineation of the postsurgical lumpectomy cavity,” 67(5)Int J Radiat Oncol Biol Phys 1299-308 (2007)) have documented thedifficulty in delineating the cavity boundaries to be targeted in thepostoperative period. Landis et al also document the range of sizes andshapes and geometric uncertainties that can be typically seen in theclinical environment. Tissue margins can be difficult to delineate dueto uncertainty about the extent and position of the excision cavity andits adjacent tissue. Therefore, a device of the present invention thatis placed into the surgical cavity at the time of cavity resection willdemarcate these tissue boundaries at the time the cavity is surgicallycreated, so that postoperatively (e.g. during the imaging required forsubsequent radiation therapy) the tissue boundaries are much easier toidentify (or identified with higher confidence as to their configurationand specific location). In some clinical environments, only the markerclips of the device will be visible and in other cases, thebioabsorbable carrier material may also be visible in addition to themarker clips. In either case, a more accurate delineation of the tissueadjacent to the lumpectomy cavity can be documented than would bepossible had the marker device of the present invention not been placed,or had individual discrete marking devices (e.g. clips) been placed intothe cavity as an alternative.

Following tumor resection, an implant of the invention (using any of theembodiments described herein) is placed into the tumor resection cavity104. Placement can occur prior to closing the surgical site 102 suchthat the surgeon intra-operatively places the device, or alternatively,a device can be inserted after the initial surgical resection (e.g.,during a re-excision to remove more tissue due to positive or inadequatesurgical margins). In some cases, a new incision for introduction of thedevice may be created. In either case, the device, whose peripheralsurface is preferably sized and configured to reproducibly demarcate thetissue surrounding the resection cavity 104, is placed within theresected tissue cavity.

In some cases, it may be useful to employ a sizing tool in order to helpthe clinician choose the proper size and shape of device to be implantedfor a given surgical cavity. It is particularly useful for the sizingtool to represent not only a similar general size (e.g. width andlength) of the device to be implanted, but also to represent the generaldevice configuration and/or device flexibility as well. With theseattributes in mind, a sizing tool 92 is shown in FIGS. 16A and 16B. Theexemplary sizing tool 92 includes a handle portion 94 and a sizingportion 96 that represents the size of a particular size of implantabledevice. Alongside the sizing tool 92 in the figure is an implantabledevice 10 that is represented by the sizing tool. FIG. 16C shows anarray of such sizing tools 92 with their correspondingly sized andshaped implantable marker devices 10. In use, prior to selecting thespecific size and shape of marker to implant, the clinician chooses aparticular sizing tool from a set of reusable sterile sizing tools, suchas that shown in FIG. 16C. While holding the handle of the sizing tool,the clinician places the spheroid end of the sizing tool into thesurgical cavity. If desired, the tissue surrounding the tool may besurgically approximated by one or more temporary stitches or staples, togive the clinician a sense of how the tissue interacts with the sizingtool and hence how the tissue will interact around the implantablemarker device. If the particular size or shape of the sizing tool is notoptimal for the desired characteristics (e.g. wound tension, tissuecavity conformance), an alternately sized or shaped sizing tool may beused until the desired interaction with the surrounding tissue isachieved. Subsequently, the sizing tool is removed from the wound andthe clinician selects the implant device that most closely matches thesizing tool configuration, and then places the implant device in thetissue cavity. Subsequently the breast tissue interacts with the implantin a fashion predicted by the sizer tool and the clinician closes theskin incision.

Following insertion of the implant device, such as by an open method orusing a mini-open (e.g. tunneling) approach, the implant occupies (atleast a portion of) the tissue cavity 104 and demarcates the surroundingtarget tissue until such time as the implant resorbs. When theimplantable device is implanted in a resection cavity in soft tissue, asubstantial portion of the device can conform to the walls of theresection cavity. “Substantial portion” is used herein in this contextto mean greater than or equal to about 25% of the outward facing surfaceof the implant is in direct apposition to the surrounding tissue. Giventhe irregularities of many lumpectomy cavity shapes, not all of thesurface of the implant may be in direct apposition to the surroundingtissue. Depending upon a variety of factors such as anatomy and surgicaltechnique, there may often be voids filled by air or seroma. In someembodiments and clinical cases, the implant fully conforms to thesurrounding tissue—where fully conforms means greater than or equal toabout 95% of the implant's surface will be in direct apposition tosurrounding tissue. Regardless of the percent of the device outersurface that comes in contact with the surrounding tissue, because ofthe open architecture of the device, there typically remains a portionof the resection cavity inner surface that does not come into contactwith the implanted device. Otherwise the devices would not be of theopen-architecture design, where there is free communication of fluidsand tissue across the peripheral boundary of the device afterimplantation.

With the use of our invention, a defined tissue region is provided sothat radiation can more accurately be delivered to the previouslyirregular or indeterminate tissue cavity walls. This defined surface canbe delineated via a variety of imaging modalities such as ultrasound,MRI and CT or other x-ray by the bioabsorbable portion of the device orby the marker clips, or by both. In addition, the device may help reduceerror in the treatment procedure introduced by tissue movement. Thepositioning and stabilization provided by the implant device may greatlyimprove the effectiveness of radiation therapy by facilitating radiationdosing and improving its accuracy. The result is a treatment methodwhich concentrates radiation on target tissue and helps to minimizedamage and preserve the surrounding healthy tissue. When the radiationdose is more precisely delivered, lower dose can be delivered toadjacent normal tissue, which improves the suitability for acceleratedradiation treatment regimens (e.g., fewer dose fractions at a higherdose rate).

Prior to delivering radiation, but after placing the implant device, thedevice and the surrounding target tissue can preferably be visualizedwith an imaging device, including by way of non-limiting example, x-ray(kV or MV), conventional (2-D) mammography, 3-D mammography (includingmammographic tomosynthesis, e.g., SELENIA Tomosynthesis by Hologic,Inc.), ultrasound, MRI, CT scan, PET, SPECT, and combinations thereof.These imaging devices provide a picture of the implant device and thesurrounding target tissue to assist with the planning of externalradiation therapy. Thus, the device can delineate the cavity boundariesso that a target volume may be derived. The device then provides atarget for more accurate repositioning of the patient's targeted tissueimmediately prior to each fraction of treatment. Finally, it can providea means of real-time tracking the motion of the target volume so thatthe beams can either move with the target, can reshape dynamically toconform to a moving target or can be turned on and off as the targetmoves out of and back into the beams' path.

In the case of external beam radiation therapies such asthree-dimensional conformal radiation therapy (3DCRT) and IMRT, theimaging procedures provide a map of the residual tissue margin andassist with targeting tissue for radiation dosing. The radiation beamsare then adapted for delivering a very precise radiation dose to thetarget tissue. Also, the improved targeting capability reduces thepatient setup errors (target positioning relative to the treatmentbeam). Both factors improve target tissue conformality, reduce theradiation exposure to normal tissues surrounding the targeted volume ofthe body, and can allow for smaller target volumes than would otherwisebe prescribed due to the decrease in uncertainty of the tissue marginsof the cavity.

Some treatment regimens require repeated radiation dosing over a courseof days or weeks, and the device can be used in those cases torepeatedly position the tissue surrounding the resected tumor cavity.These steps can be repeated as necessary over the course of a treatmentregimen. Preferably, the implanted device remains in place withoutintervention, i.e., without removal or actions to change itsconfiguration, throughout the course of treatment.

While the specific examples provided relate to treatment of cancer inthe breast, the devices and procedures described herein may be used forother anatomic sites as well, (e.g. muscle for sarcoma, liver for livertumors) including any regions where tissue is removed and the patientmay require targeted radiation treatment at or near the site of tissueremoval. The device may also be placed in the cavity created by the opensurgical biopsy of high risk non-cancerous or ultimately benign breastlesions as well as other non-cancerous tissue sites. Doing so identifiesthe cavity for future breast imaging studies, which can be useful forlong-term patient monitoring.

In addition to the 3-dimensional structures that have been described,there is also a clinical need to provide relatively 2-dimensionalversions of the device as well. Whereas the 3-D devices demarcate theboundaries of more 3 dimensional structure (e.g., lumpectomy cavity)these 2-D devices may be more useful to demarcate the more planar orcurvilinear boundaries of tissue that may arise from surgical excision(e.g., during breast reduction).

Such planar yet compliant and conformable versions are shown in FIGS. 4,5, and 17. These designs are useful for identifying the tissueboundaries that ultimately are re-approximated, actively or passively,during various surgical procedures. The surgical procedures that maybenefit from these 2-dimensional designs are procedures that requireexcision of soft tissue followed by reapproximation of the resectionboundaries (e.g., as in breast reduction or lung-wedge resections).

FIGS. 4 and 5 illustrate a spiral planar form of a 2-D style marker thatcan be placed surgically into a region of tissue that can be surgicallyapproximated. The spiral elements are free to flex to conform to thetissue planes as the tissue is surgically approximated.

FIG. 17A illustrates another embodiment 10 e comprising an array offlexible spines 112 made of a bioabsorbable polymer emanating from acentral region 114. A radiopaque marker 28 of the type describedpreviously resides at the extremity of each of the spines. A marker clipmay reside at the central region as well (not shown). In use, the deviceis placed at the time of surgery along the surface of the region oftissue to be approximated. In many cases the tissue surfaces can beirregular in surface shape (e.g., non-planar) and so as the tissuesurfaces may be approximated (e.g., by surgical suturing) yet the deviceis still able to flex and conform to the irregular surface shapes of thetissue surfaces. Again the open architecture of this structure allowsfor unencumbered fluid passage and tissue mobility while stilldemarcating the excised issue boundaries.

FIG. 17B illustrates yet another embodiment 10 f similar to the devicedescribed with respect to FIG. 17A except that the central region 116 isa linear spine like element, which is also made of bioabsorbablematerial. Marker elements reside not only on the peripheral spines butalso at periodic intervals along the central spine of the device. In usethe device may be cut at various locations along the spine to best fitthe anatomical site it is to be placed, prior to placement at the tissuesite.

FIG. 18 illustrates yet another embodiment 10 g where the device iscomprised of a flexible bioabsorbable mesh or screen 118 that containmarker 28 elements that reside fixedly to the periphery or otherlocations along the flexible plane. In this embodiment radiopaquemarkers are comprised of Titanium wire elements that envelop thefilaments of the mesh or screen material. In other embodiments (notshown), the wire elements may be enveloped within the bioabsorbablematerial and oriented either parallel or perpendicular to the generallyplanar flexible surface of the embodiment (as shown in FIG. 4B). Oneadvantage of the perpendicular marker elements is that the markerelements may partially embed (like cleats of a shoe sole) into theadjacent tissue to secure the position of the device along the surfaceof the tissue to be approximated.

A person of ordinary skill in the art will appreciate further featuresand advantages of the invention based on the above-describedembodiments. Accordingly, the invention is not to be limited by what hasbeen particularly shown and described, except as indicated by theappended claims or those ultimately provided. All publications andreferences cited herein are expressly incorporated herein by referencein their entirety, and the invention expressly includes all combinationsand sub-combinations of features included above and in the incorporatedreferences.

1-31. (canceled)
 32. An implantable device for targeting external beamradiation to a three dimensional target tissue volume surrounding alumpectomy cavity comprising: a body, the body (i) having a periphery;(ii) being formed of a bioabsorbable polymer; (iii) having a pluralityof radiopaque markers attached to the body around the periphery; and(iv) being sized and configured so as to place the radiopaque markers inposition to define the three dimensional target tissue volume; whereinthe body includes spaced apart elements that define an open architecturethat permits partial encapsulation of the cavity wall around theelements upon initial placement of the implantable device within thecavity while the radiopaque markers remain in position for targeting thethree dimensional target tissue volume; and wherein the body defines avolume that is spherical or ellipsoid in shape and has a diameterbetween 2 cm and 5 cm.
 33. (canceled)
 34. The device of claim 32,wherein the body provides a desired shape to the cavity wall whileallowing compliance and conformability to provide increased comfort fora patient.
 35. The device of claim 32, wherein the radiopaque markerscomprise metallic clips.
 36. The device of claim 32, wherein theradiopaque markers are attached around the periphery so as to definethree orthogonal axes.
 37. The device of claim 32, wherein at least someof the radiopaque markers are differentiated to create an asymmetry thatis observable during imaging in order to determine the orientation ofthe implantable device.
 38. (canceled)
 39. The device of claim 32,wherein the bioabsorbable polymer has an absorption time of at least 2weeks.
 40. The device of claim 39, wherein the device having a bodyformed of a bioabsorbable polymer remains functional for at least 6months.
 41. The device of claim 32, wherein the bioabsorbable polymer isthermoplastic.
 42. (canceled)
 43. The device of claim 32, furthercomprising one or more protrusions for bluntly penetrating intosurrounding tissue.
 44. The device of claim 32, wherein the body is madeup of a plurality of elements.
 45. (canceled)
 46. (canceled)
 47. Thedevice of claim 32, wherein the radiopaque markers allow visualizationby radiography.
 48. The device of claim 47, wherein the radiographyincludes mega-voltage x-rays.
 49. The device of claim 47, wherein theradiography includes kilo-voltage x-rays.
 50. The device of claim 47,wherein the radiography includes fluoroscopy.
 51. An implantable devicefor targeting external beam radiation to regions of target tissuesurrounding a tumor resection cavity comprising: a body, the body havinga periphery and being formed of a bioabsorbable material; and aplurality of radiopaque markers attached to the body around theperiphery; wherein the body defines an open architecture that supports awall of the cavity yet also permits partial encapsulation of the cavitywall around the body upon initial placement of the implantable devicewithin the cavity; and wherein the body defines a volume that isspherical or ellipsoid in shape and has a diameter between 2 cm and 5cm.
 52. The device of claim 51, wherein the radiopaque markers comprisesurgical clips.
 53. The device of claim 51, wherein the radiopaquemarkers are attached around the periphery so as to define threeorthogonal axes.
 54. The device of claim 51, wherein the bioabsorbablematerial is a thermoplastic polymer.
 55. (canceled)
 56. The device ofclaim 51, further comprising one or more protrusions for bluntlypenetrating into surrounding tissue.
 57. The device of claim 51, whereinthe body is made up of a plurality of elements.
 58. The device of claim51, wherein at least some of the radiopaque markers are differentiatedto create an asymmetry that is observable during imaging in order todetermine the orientation of the implantable device.
 59. The device ofclaim 51, wherein the bioabsorbable material has an absorption time ofat least 2 weeks.
 60. The device of claim 59, wherein the device havinga body formed of a bioabsorbable material remains functional for atleast 6 months.
 61. The device of claim 51, wherein the body provides adesired shape to cavity wall while allowing compliance andconformability to provide increased comfort for a patient.